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Taking thyroid drugs—is timing important?

Posted by medconsumers on January 24, 2011

People on thyroid medicine are typically told to take it in the morning on an empty stomach. Turns out this advice is based on zero evidence. Now bedtime is considered the better choice, according to the first placebo vs. thyroid drug trial to look at timing.

All of the study participants had hypothyroidism, aka an underactive thyroid, which means that the thyroid gland does not make enough thyroid hormones. The standard treatment is replacement with a drug called levothyroxine. This is the chemical, or generic, name for the synthetic version of the thyroid’s principle hormone. The drug can be prescribed generically or under several brand names, such as Synthroid, Levoxyl, Levothroid, and Unithroid.

Dutch researchers led by Nienke Bolk, MD, wanted their study to answer two questions: Does levothyroxine taken just before going to bed rather than the morning improve thyroid hormone levels? Will the change in timing have any major effects on health and quality of life? The second question is just as important because hypothyroidism is known to be associated with fatigue, weight gain, cold intolerance, depression, among many other things. And it can have a negative effect on risk factors like high cholesterol.

The study participants were recruited after seeking care for hypothyroidism at Maasstad Hospital Rotterdam in the Netherlands. For the first three months of the study, the participants were given lookalike capsules and instructed to take one in the morning and one at bedtime (one levothyroxine, the other a placebo). For the next three months, those taking levothyroxine in the morning were switched to placebo capsules and vice versa for the rest who had been on a morning placebo.

Throughout the trial the participants did not know when they were taking the real drug. At six week intervals, blood samples were taken along with measurements of blood pressure, heart rate, and body weight. All participants completed quality-of-life questionnaires.

The study, published in the Archives of Internal Medicine, concluded that levothyroxine taken at bedtime significantly improved thyroid hormone levels. They increased when participants took the drug at bedtime and decreased when taken in the morning.

Dr. Bolk and colleagues were not sure why bedtime was the better choice, but offered several possibilities. It could be due to the fact that levothyroxine is absorbed better in the G.I. tract which typically slows down at night several hours after dinner. (Many of the study participants reported that they do not have snacks between dinner and bedtime.) And perhaps there is less interference by breakfast, albeit delayed a half to full hour, or other medications usually taken in the morning.

The change in timing from morning to bedtime had no negative effects on the participants’ quality of life, e.g., fatigue or physical functioning, or risk factors, e.g., high cholesterol. But an interesting contradiction came up after the trial was over and the study participants were told when they had been taking levothyroxine. Checking back with their questionnaires filled out during the study, 34 of the 90 participants said they felt better during the period of morning intake of levothyroxine; 31 preferred bedtime intake; and 25 had no preference.

When convenience is taken into consideration, bedtime would be favored by those who don’t like to postpone breakfast.

Maryann Napoli, Center for Medical Consumers©

4 Responses to “Taking thyroid drugs—is timing important?”

  1. Do any of the studies of synthetic thyroid hormone apply to the natural hormone, Armour’s ?

  2. Pat de la Fuente said

    I’m sorry that the doctors who conducted the study on levothyroxine focused on the timing of the dose, without questioning whether or not the drugs actually benefitted the participants’ health and quality of life. Although levothyroxine will “improve hormone levels” on lab tests, we need to question why people who are asymptomatic–who do not report experiencing fatigue, weight gain, cold intolerance and depression–are routinely given a drug for their hypothyroidism. Levothyroxine, under its various trade names, is one of the most widely prescribed drugs in the U.S. Is there an epidemic of hypothyroidism and, if so, what if any are the health effects of this supposedly dread disease?

    • medconsumers said

      Pat asks an important question about the proven benefit of levothyroxine. Should it be prescribed to symptomless people with test results that indicate early-stage hypothyroidism (i.e., subclinical hypothyroidism)? Here’s a summary of the Cochrane review on this topic. The short answer is: There is no evidence for this common practice. For a Cochrane review, authors evaluate the best studies to answer such questions as: Does this treatment work? And for whom? For the levothyroxine review, the authors could find only a few studies with a combined total of 350 participants. The studies found no benefit to treating symptomless people with hypothyroidism in terms of increased survival or lower risk of stroke or heart attack. Though people are expected to go on thyroid replacement therapy for life, no study lasted more than 14 months! “Adverse effects were inadequately studied…especially in older patients”! Shocking, considering that this is one of the most commonly prescribed drugs in the country.

      This Cochrane review is five years old. Nothing of importance seems to have been published since. However, here’s a noteworthy excerpt from a 2009 paper on subclinical hypothyroidism in Mayo Clinic Proceedings: “The possibility that it [subclinical hypothyroidism] is a cardiovascular risk factor has been a subject of debate. Large-scale randomized studies are needed for evidence-based recommendations regarding screening for mild thyroid failure and levothyroxine therapy for this condition.” To browse Cochrane reviews on other topics, click here.

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